The Suppressor of cytokine signaling (SOCS) and cytokine-inducible SH2 proteins are a family of intracellular proteins which regulate the immune cell responses to cytokines. SOCS1 acts to suppress dendritic cell (DC) as well as T cell hyperactivation following cytokine signaling by inhibiting JAK tyrosine kinase, a kinase necessary for type I and II cytokine receptors to initiate signaling, by directly binding to the catalytic domain of the kinase. SOCS1 also possesses E3 ubiquitin protein ligase activity that results in the polyubiquitination of its target proteins and subsequent degradation by the proteosome. It is through this method that SOCS1 negatively regulates signaling by Toll-like receptors TLR2 and TLR4 by mediating the degradation of the TLR signaling adaptor protein TIRAP.
